The central theme of this program grant is regulation of gene expression by oncogenes. We will address this theme by (a) isolation of new oncogenes, (b) study of the regulation of known oncogenes, (c) study of the mechanism by which oncogenes can affect transcription of other genes, (d) definition and purification of factors which regulate promoters, and (e) identification of factors which recognize enhancer elements in a cell type specific fashion. The exciting new aspect of this theme is that part of the problem of cancer can now be phrased in the context of the action and control of known genes. At the moment, the set of oncogenes that have been identified number about 25-30. These genes are probably involved in essential cellular processes and are altered in transformed cells in terms of either level of activity or type of activity. The next frontier in research on oncogenesis is to determine how these oncogene proteins function biochemically and affect alterations in cell behavior. This is a challenging problem as little is known about the cellular processes, particularly nuclear processes, that regulate cell growth. Success in this endeavor will require the close interaction and collaboration of scientists interested in: the action of oncogenes, the intracellular signals generated by peptide hormones, the regulation of gene expression and the biochemistry of nuclear processes such as transcription. Understanding the activities of oncogenes at this molecular level will reveal how they collaborate in transformation and the relationships of transformation to processes such as differentiation